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Gentamicin and Gram-Negative Bacteremia. A Synergism for the Development of Experimental Nephrotoxic Acute Renal Failure
0022-534 7/86/1365-1155$02.00/0 Vol. 136, November
THE JOURNAL OF UROLOGY
Copyright© 1986 by The Williams & Wilkins Co.
Printed in U.S.A.
ABSTRACTS INFECTIONS AND ANTIBIOTICS Acute Renal Failure Associated With Acute Pyelonephritis and Consumption of Non-Steroidal Anti-Inflammatory Drugs L. K. ATKINSON, T. H.J. GOODSHIP AND M. K. WARD, Renal Unit, Royal Victoria Infirmary, Newcastle upon Tyne, England
Brit. Med. J., 292: 97-98 (Jan. 11) 1986 Acute renal failure is seen in patients with pre-existing renal disease and acute pyelonephritis. The use of nonsteroidal antiinflammatory agents in a patient with a urinary tract infection also may produce impairment of renal function. Discontinuation of the anti-inflammatory agent results in improved renal function. The 4 cases presented tend to support the hypothesis. The authors proffer some interesting concepts concerning the mechanisms involved. J. A. A. 3 references
Gentamicin and Gram-Negative Bacteremia. A Synergism for the Development of Experimental Nephrotoxic Acute Renal Failure R. A. ZAGER AND R. B. PRIOR, Departments of Medicine, The
University of Washington, Seattle, Washington and Ohio State University, Columbus, Ohio J. Clin. Invest., 78: 196-204 (July) 1986 To explore whether bacteremia potentiates gentamicin nephrotoxicity the authors injected rats with either 1 X 109 Escherichia coli, Pseudomonas aeruginosa or Staphylococcus aureus, and then gave them 100 mg./kg. gentamicin. Renal injury was assessed during the next 24 to 48 hours. Staphylococcus/gentamicin or gentamicin alone induced no renal injury. However, E. coli/gentamicin and P. aeruginosa/gentamicin caused acute renal failure (severe azotemia, tubular necrosis and cast formation). This effect was not owing to acute reductions in arterial blood pressure or renal blood flow, it could be reproduced by substituting nonviable for viable gram-negative organisms and it was associated with increased renal gentamicin uptake. E. coli without gentamicin induced only mild azotemia and no tubular necrosis. Endotoxin-tolerant rats were significantly protected against the E. coli/gentamicin nephrotoxic interaction. The authors conclude that gram-negative bacteremia and gentamicin exert synergistic nephrotoxicities and that this effect is mediated, at least in part, by endotoxin and by increased renal gentamicin uptake. G. P. M. 6 figures, 3 tables, 18 references
Prospects of Therapy for Infections With Human TLymphotropic Virus Type III
M. S. HIRSCH AND J. C. KAPLAN, Departments of Medicine and Microbiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts Ann. Intern. Med., 103: 750-755 (Nov.) 1985
Attempts have been made in the past to control various human viral infections. Significant success has been achieved in controlling polio, smallpox, measles, mumps and rubella by the use of vaccines. More recently, effective vaccines have been developed for hepatitis B, rabies and varicella virus infections, and a variety of antiviral drugs have become available for some viral infections. Efforts are being made to develop specific antiviral drugs and possible vaccine against human T-lymphotropic virus type III (HTLV-III). The virus is susceptible to attack by antiviral agents at various locations during its replication cycle. In vitro activity against the HTLV-III has been demonstrated by inhibitors of reverse transcriptase activity, which is involved in its replicative cycle. The drugs belonging to this group include suramin, antimoniotungstate (HPA-23) and trisodium phosphonoformate. Early clinical trials have shown encouraging results. Other agents that have shown significant antiviral activity are recombinant a-A-interferon, ribavirin and ansamycin. In general, interferons show broad-spectrum activity against deoxyribonucleic and ribonucleic acid viruses. a-Interferon has antiviral activity against herpes zoster, herpes labialis, hepatitis B and laryngeal papillomatosis. Recombinant ainterferon has shown activity against Kaposi's sarcoma in patients with the acquired immunodeficiency syndrome (AIDS). Double-blind clinical trials with recombinant a-Ainterferon are underway to evaluate its efficacy in AIDS and AIDS-related complex. Attempts are being made to develop vaccines and passive neutralizing antiserum against HTLV-111. A variety of immunomodulators, such as interleukin-2, and thymic humoral factors are being evaluated. A combination of immunomodulator and antiviral agents administered for sufficient length of time may prove to be effective in controlling infection with RTL VIII. N. S. D. 1 figure, 1 table, 50 references
ONCOLOGY AND CHEMOTHERAPY Clinically Unsuspected Pheochromocytomas. Experience at Henry Ford Hospital and a Review of the Literature N. K. KRANE, Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan
Arch. Intern. Med., 146: 54-57 (Jan.) 1986 Of 32 confirmed cases of pheochromocytoma diagnosed between 1951 and 1982, 11 (34 per cent) were not diagnosed clinically. Of the 15 cases seen before 1962, 8 were not suspected, compared to only 3 of 17 seen after 1962. A high index of suspicion is most helpful to make the diagnosis of pheochromocytoma. Newer methods in use since 1962 make diagnosis more likely. There are newer, highly sensitive and accurate assays for catecholamine (and metabolites) in plasma and urine. With plasma and urine levels, and imaging techniques (1 31 iodine-metaiodobenzylguanine for scintigraphy) preoperative diagnosis will be correct. J. A. A. 2 tables, 41 references
1155
THE JOURNAL OF UROLOGY
Copyright© 1986 by The Williams & Wilkins Co.
Printed in U.S.A.
ABSTRACTS INFECTIONS AND ANTIBIOTICS Acute Renal Failure Associated With Acute Pyelonephritis and Consumption of Non-Steroidal Anti-Inflammatory Drugs L. K. ATKINSON, T. H.J. GOODSHIP AND M. K. WARD, Renal Unit, Royal Victoria Infirmary, Newcastle upon Tyne, England
Brit. Med. J., 292: 97-98 (Jan. 11) 1986 Acute renal failure is seen in patients with pre-existing renal disease and acute pyelonephritis. The use of nonsteroidal antiinflammatory agents in a patient with a urinary tract infection also may produce impairment of renal function. Discontinuation of the anti-inflammatory agent results in improved renal function. The 4 cases presented tend to support the hypothesis. The authors proffer some interesting concepts concerning the mechanisms involved. J. A. A. 3 references
Gentamicin and Gram-Negative Bacteremia. A Synergism for the Development of Experimental Nephrotoxic Acute Renal Failure R. A. ZAGER AND R. B. PRIOR, Departments of Medicine, The
University of Washington, Seattle, Washington and Ohio State University, Columbus, Ohio J. Clin. Invest., 78: 196-204 (July) 1986 To explore whether bacteremia potentiates gentamicin nephrotoxicity the authors injected rats with either 1 X 109 Escherichia coli, Pseudomonas aeruginosa or Staphylococcus aureus, and then gave them 100 mg./kg. gentamicin. Renal injury was assessed during the next 24 to 48 hours. Staphylococcus/gentamicin or gentamicin alone induced no renal injury. However, E. coli/gentamicin and P. aeruginosa/gentamicin caused acute renal failure (severe azotemia, tubular necrosis and cast formation). This effect was not owing to acute reductions in arterial blood pressure or renal blood flow, it could be reproduced by substituting nonviable for viable gram-negative organisms and it was associated with increased renal gentamicin uptake. E. coli without gentamicin induced only mild azotemia and no tubular necrosis. Endotoxin-tolerant rats were significantly protected against the E. coli/gentamicin nephrotoxic interaction. The authors conclude that gram-negative bacteremia and gentamicin exert synergistic nephrotoxicities and that this effect is mediated, at least in part, by endotoxin and by increased renal gentamicin uptake. G. P. M. 6 figures, 3 tables, 18 references
Prospects of Therapy for Infections With Human TLymphotropic Virus Type III
M. S. HIRSCH AND J. C. KAPLAN, Departments of Medicine and Microbiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts Ann. Intern. Med., 103: 750-755 (Nov.) 1985
Attempts have been made in the past to control various human viral infections. Significant success has been achieved in controlling polio, smallpox, measles, mumps and rubella by the use of vaccines. More recently, effective vaccines have been developed for hepatitis B, rabies and varicella virus infections, and a variety of antiviral drugs have become available for some viral infections. Efforts are being made to develop specific antiviral drugs and possible vaccine against human T-lymphotropic virus type III (HTLV-III). The virus is susceptible to attack by antiviral agents at various locations during its replication cycle. In vitro activity against the HTLV-III has been demonstrated by inhibitors of reverse transcriptase activity, which is involved in its replicative cycle. The drugs belonging to this group include suramin, antimoniotungstate (HPA-23) and trisodium phosphonoformate. Early clinical trials have shown encouraging results. Other agents that have shown significant antiviral activity are recombinant a-A-interferon, ribavirin and ansamycin. In general, interferons show broad-spectrum activity against deoxyribonucleic and ribonucleic acid viruses. a-Interferon has antiviral activity against herpes zoster, herpes labialis, hepatitis B and laryngeal papillomatosis. Recombinant ainterferon has shown activity against Kaposi's sarcoma in patients with the acquired immunodeficiency syndrome (AIDS). Double-blind clinical trials with recombinant a-Ainterferon are underway to evaluate its efficacy in AIDS and AIDS-related complex. Attempts are being made to develop vaccines and passive neutralizing antiserum against HTLV-111. A variety of immunomodulators, such as interleukin-2, and thymic humoral factors are being evaluated. A combination of immunomodulator and antiviral agents administered for sufficient length of time may prove to be effective in controlling infection with RTL VIII. N. S. D. 1 figure, 1 table, 50 references
ONCOLOGY AND CHEMOTHERAPY Clinically Unsuspected Pheochromocytomas. Experience at Henry Ford Hospital and a Review of the Literature N. K. KRANE, Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan
Arch. Intern. Med., 146: 54-57 (Jan.) 1986 Of 32 confirmed cases of pheochromocytoma diagnosed between 1951 and 1982, 11 (34 per cent) were not diagnosed clinically. Of the 15 cases seen before 1962, 8 were not suspected, compared to only 3 of 17 seen after 1962. A high index of suspicion is most helpful to make the diagnosis of pheochromocytoma. Newer methods in use since 1962 make diagnosis more likely. There are newer, highly sensitive and accurate assays for catecholamine (and metabolites) in plasma and urine. With plasma and urine levels, and imaging techniques (1 31 iodine-metaiodobenzylguanine for scintigraphy) preoperative diagnosis will be correct. J. A. A. 2 tables, 41 references
1155